Research

Current Projects
The sporulation process of B. subtilis is one of the most well characterized molecular genetic systems available for the analysis of postexponential phase regulatory mechanisms. Over 100 genes have been identified and assigned to genetic loci, mutations in which specifically block sporulation at a defined morphological and biochemical stage of development. In many cases the nature and cellular function of the gene product is known.

Recent studies of the sporulation initiation control mechanism suggest that development is triggered by a dedicated, nutrient deprivation sensing system, which in turn activates a transcriptional switch consisting of trans-acting phosphoprotein auxiliary transcription factors. We are analyzing the functional interactions required for the generation of a starvation signal and the interactions between transition state regulators that allow the cell to switch from a "vegetative" to a "postexponential" pattern of global gene expression.

The regulation of sporulation-specific gene expression is under intensive transcriptional and translational control. Multiple RNA polymerase minor sigma factors are involved in regulating stage-specific sporulation gene expression. We have isolated mutations in RNA polymerase core subunits which interfere with developmentally-specific gene expression. We have identified mutations in six ribosomal protein and elongation factor genes which also block sporulation at a variety of developmental stages. We have identified extragenic suppressor mutations that are able to rescue all of these transcriptional and translational developmental defects. These mutations have defined a new gene that couples postexponential transcription/translation processes.

We are utilizing genomic, computational and phylogenetic techniques to reconstruct the genesis and evolution of endospore formation in two genera: Clostridium and Bacillus. The mechanisms, mode and tempo of sporulation gene set evolution are being studied in the context of ecogenetic and developmental selection.

Several related research efforts are focused on understanding the structure and function of the bacterial endospore. These projects involve: (1) identifying the molecular genetic determinants of spore and cell surface structure and function; (2) determining the environmental and genetic mechanisms that regulate the abundance and distribution of spore structures; (3) determining the mechanisms governing the germination of spores; (4) and identifying spore/cell surface proteins that could improve the antigenic composition of vaccines. We are also interested in understanding the chemical cues that trigger spore formation and germination, and identifying inhibitors of the spore germination processes.